The current proposal aims to test the hypothesis that some of the biological changes seen in the course of normal aging, if they occur at an earlier time of life, can contribute to the development of Primary Degenerative Dementia (PDD). Specifically, we will explore whether some age-associated biological changes: 1) happen precociously and therefore are presented to a much greater extent in PDD, especially in the early onset (presenile) dementia, and 2) are correlated with the severity of cognitive impairment in demented subjects. Measurement of biological changes. We propose to evaluate three possible biological markers: 1) Rate of melatonin synthesis (assessed by determination of blood melatonin and urine 6-hydroxymelatonin), 2) activity of the hypothalamic-pituitary-adrenal (HPA) axis (assessed by blood cortisol resistance to suppression by dexamethasone), and 3) monoamine oxidase (MAO) B-type activity (assessed by blood platelet MAO activity). Measurement of cognitive function. We will use the neuropsychological evaluation described under "Methods." Subjects. Patients with early (before 65 years of age) and late (after 65) onset of PDD and age-sex-matched normal volunteers will be studied. This proposal represents the revised version of the original project, which was approved but not funded (priority scores, 193). It was recommended that preliminary data be developed by studying MAO and melatonin in a small group of patients and age-matched controls. Results of the study may lead to a better understanding of the biological methanisms of the development of PDD. The long-term objective of the project is the potential development of objective predictors of risk for PDD. Specifically, it is hoped that assessment of pineal-HPA axis and MAO-B activity may be used as laboratory aids in the early detection of an individual at-risk. We also hope that the results obtained will help to develop a rational biological treatment of PDD.